Tomei has appeared in a number of successful movies, including What Women Want (2000), Anger Management (2003), Wild Hogs (2007), and Parental Guidance (2012).Other films include Untamed Heart (1993), Only You (1994), The Paper (1994), Unhook the Stars (1996), Slums of Beverly Hills (1998), Before the Devil Knows You're Dead (2007), Cyrus (2010), Love Is Strange (2014) and The Big Short (2015).
She also made an appearance on The Simpsons as movie star Sara Sloane, who falls in love with Ned Flanders.
Former Saturday Night Live cast member Jay Mohr wrote in his book Gasping for Airtime that, as guest host in October 1994, Tomei insisted that a proposed sketch, "Good Morning Brooklyn", not be used because she did not like the idea of being stereotyped; that stand displeased the writers and performers, given the show's penchant for satirizing celebrities. Tomei appeared in the 2000 film What Women Want, which was a commercial success, and had a supporting role in the romantic comedy Someone Like You.
She then appeared in Nick Cassavetes's Unhook the Stars.
Of Tomei's performance, The New York Times wrote, "Ms.
In 1996, she made a guest appearance on the sitcom Seinfeld, playing herself in the two-part episode "The Cadillac".
In the episode, George Costanza attempts to get a date with her through a friend of Elaine Benes'.
She also portrays Aunt May in the Marvel Cinematic Universe, having appeared in Captain America: Civil War (2016), Spider-Man: Homecoming (2017), Avengers: Endgame (2019), and Spider-Man: Far From Home (2019). She was formerly involved with the Naked Angels Theater Company and appeared in plays, such as Daughters (1986), Wait Until Dark (1998), Top Girls (2008), for which she received a nomination for the Drama Desk Award for Outstanding Featured Actress in a Play, and The Realistic Joneses (2014), for which she received a special award at the Drama Desk Awards.
While there, she became captivated by the Broadway shows to which her theater-loving parents took her and was drawn to acting as a career.
Tomei also shared a Screen Actors Guild Award nomination for Outstanding Performance by a Cast.
In 2002, she appeared in the Bollywood-inspired film The Guru and voiced the role of Bree Blackburn, the main antagonist in the animated feature film The Wild Thornberrys Movie.
Tomei did, however, parody her role from My Cousin Vinny, which had considerable Brooklyn influence, in a skit (out of several recurring) spoofing the 1995 O. In 2001, Tomei appeared in Todd Field's Best Picture nominee In the Bedroom, earning several awards including a Sho West Award for Best Supporting Actress in 2002.